ID PDGFC_HUMAN Reviewed; 345 AA. AC Q9NRA1; B4DU34; B9EGR8; Q4W5M9; Q9UL22; DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 2. DT 24-JAN-2024, entry version 161. DE RecName: Full=Platelet-derived growth factor C; DE Short=PDGF-C; DE AltName: Full=Fallotein; DE AltName: Full=Spinal cord-derived growth factor; DE Short=SCDGF; DE AltName: Full=VEGF-E; DE Contains: DE RecName: Full=Platelet-derived growth factor C, latent form; DE Short=PDGFC latent form; DE Contains: DE RecName: Full=Platelet-derived growth factor C, receptor-binding form; DE Short=PDGFC receptor-binding form; DE Flags: Precursor; GN Name=PDGFC; Synonyms=SCDGF; ORFNames=UNQ174/PRO200; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Uterus; RX PubMed=11004490; DOI=10.1016/s0167-4781(00)00066-x; RA Tsai Y.J., Lee R.K., Lin S.P., Chen Y.H.; RT "Identification of a novel platelet-derived growth factor-like gene, RT fallotein, in the human reproductive tract."; RL Biochim. Biophys. Acta 1492:196-202(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=10858496; DOI=10.1016/s0014-5793(00)01640-9; RA Hamada T., Ui-Tei K., Miyata Y.; RT "A novel gene derived from developing spinal cords, SCDGF, is a unique RT member of the PDGF/VEGF family."; RL FEBS Lett. 475:97-102(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RC TISSUE=Lung; RX PubMed=10806482; DOI=10.1038/35010579; RA Li X., Ponten A., Aase K., Karlsson L., Abramsson A., Uutela M., RA Backstrom G., Hellstrom M., Bostrom H., Li H., Soriano P., Betsholtz C., RA Heldin C.H., Alitalo K., Ostman A., Eriksson U.; RT "PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor."; RL Nat. Cell Biol. 2:302-309(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RX PubMed=11297552; DOI=10.1074/jbc.m101056200; RA Gilbertson D.G., Duff M.E., West J.W., Kelly J.D., Sheppard P.O., RA Hofstrand P.D., Gao Z., Shoemaker K., Bukowski T.R., Moore M., RA Feldhaus A.L., Humes J.M., Palmer T.E., Hart C.E.; RT "Platelet-derived growth factor C (PDGF-C), a novel growth factor that RT binds to PDGF alpha and beta receptor."; RL J. Biol. Chem. 276:27406-27414(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RC TISSUE=Fetal brain; RA Zhao J., Liu Z., Liu T., Nilsson S., Nister M.; RT "An N-terminally truncated isoform of human PDGF-C regulates the secretion RT of full-length PDGF-C and is deregulated in renal cell carcinoma."; RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Prostate; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP TISSUE SPECIFICITY. RX PubMed=11342471; DOI=10.1161/01.cir.103.18.2242; RA Uutela M., Lauren J., Bergsten E., Li X., Horelli-Kuitunen N., Eriksson U., RA Alitalo K.; RT "Chromosomal location, exon structure, and vascular expression patterns of RT the human PDGFC and PDGFC genes."; RL Circulation 103:2242-2247(2001). RN [12] RP INDUCTION. RX PubMed=11313995; DOI=10.1038/sj.onc.1204133; RA Zwerner J.P., May W.A.; RT "PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family RT tumors."; RL Oncogene 20:626-633(2001). RN [13] RP TISSUE SPECIFICITY. RX PubMed=12176024; DOI=10.1016/s0006-291x(02)00917-8; RA Andrae J., Molander C., Smits A., Funa K., Nister M.; RT "Platelet-derived growth factor-B and -C and active alpha-receptors in RT medulloblastoma cells."; RL Biochem. Biophys. Res. Commun. 296:604-611(2002). RN [14] RP FUNCTION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING (ISOFORMS 2 AND 3), RP GLYCOSYLATION, AND MUTAGENESIS OF CYS-124. RX PubMed=11854040; DOI=10.1016/s1357-2725(01)00124-8; RA Dijkmans J., Xu J., Masure S., Dhanaraj S., Gosiewska A., Geesin J., RA Sprengel J., Harris S., Verhasselt P., Gordon R., Yon J.; RT "Characterization of platelet-derived growth factor-C (PDGF-C): expression RT in normal and tumor cells, biological activity and chromosomal RT localization."; RL Int. J. Biochem. Cell Biol. 34:414-426(2002). RN [15] RP FUNCTION. RX PubMed=12032822; DOI=10.1038/sj.onc.1205486; RA Zwerner J.P., May W.A.; RT "Dominant negative PDGF-C inhibits growth of Ewing family tumor cell RT lines."; RL Oncogene 21:3847-3854(2002). RN [16] RP DEVELOPMENTAL STAGE, AND INDUCTION. RX PubMed=12707385; DOI=10.1097/01.asn.0000062964.75006.a8; RA Eitner F., Ostendorf T., Kretzler M., Cohen C.D., Eriksson U., Grone H.J., RA Floege J.; RT "PDGF-C expression in the developing and normal adult human kidney and in RT glomerular diseases."; RL J. Am. Soc. Nephrol. 14:1145-1153(2003). RN [17] RP CHARACTERIZATION OF SECRETED ACTIVE FORM, SUBUNIT, DISULFIDE BONDS, AND RP 3D-STRUCTURE MODELING. RX PubMed=12598536; DOI=10.1074/jbc.m301728200; RA Reigstad L.J., Sande H.M., Fluge O., Bruland O., Muga A., Varhaug J.E., RA Martinez A., Lillehaug J.R.; RT "Platelet-derived growth factor (PDGF)-C, a PDGF family member with a RT vascular endothelial growth factor-like structure."; RL J. Biol. Chem. 278:17114-17120(2003). RN [18] RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=15061151; DOI=10.1161/01.atv.0000120785.82268.8b; RA Fang L., Yan Y., Komuves L.G., Yonkovich S., Sullivan C.M., Stringer B., RA Galbraith S., Lokker N.A., Hwang S.S., Nurden P., Phillips D.R., RA Giese N.A.; RT "PDGF C is a selective alpha platelet-derived growth factor receptor RT agonist that is highly expressed in platelet alpha granules and vascular RT smooth muscle."; RL Arterioscler. Thromb. Vasc. Biol. 24:787-792(2004). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PLAT. RX PubMed=15372073; DOI=10.1038/sj.emboj.7600397; RA Fredriksson L., Li H., Fieber C., Li X., Eriksson U.; RT "Tissue plasminogen activator is a potent activator of PDGF-CC."; RL EMBO J. 23:3793-3802(2004). RN [20] RP INDUCTION BY EGR1. RX PubMed=15247255; DOI=10.1074/jbc.m406063200; RA Midgley V.C., Khachigian L.M.; RT "Fibroblast growth factor-2 induction of platelet-derived growth factor-C RT chain transcription in vascular smooth muscle cells is ERK-dependent but RT not JNK-dependent and mediated by Egr-1."; RL J. Biol. Chem. 279:40289-40295(2004). RN [21] RP REVIEW. RX PubMed=16279938; DOI=10.1111/j.1742-4658.2005.04989.x; RA Reigstad L.J., Varhaug J.E., Lillehaug J.R.; RT "Structural and functional specificities of PDGF-C and PDGF-D, the novel RT members of the platelet-derived growth factors family."; RL FEBS J. 272:5723-5741(2005). RN [22] RP FUNCTION, INTERACTION WITH PLAT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ARG-231; LYS-232 AND ARG-234. RX PubMed=15911618; DOI=10.1074/jbc.m503388200; RA Fredriksson L., Ehnman M., Fieber C., Eriksson U.; RT "Structural requirements for activation of latent platelet-derived growth RT factor CC by tissue plasminogen activator."; RL J. Biol. Chem. 280:26856-26862(2005). RN [23] RP FUNCTION. RX PubMed=15389578; DOI=10.1002/jcp.20154; RA Jinnin M., Ihn H., Mimura Y., Asano Y., Yamane K., Tamaki K.; RT "Regulation of fibrogenic/fibrolytic genes by platelet-derived growth RT factor C, a novel growth factor, in human dermal fibroblasts."; RL J. Cell. Physiol. 202:510-517(2005). RN [24] RP FUNCTION. RX PubMed=15728360; DOI=10.1073/pnas.0409722102; RA Campbell J.S., Hughes S.D., Gilbertson D.G., Palmer T.E., Holdren M.S., RA Haran A.C., Odell M.M., Bauer R.L., Ren H.P., Haugen H.S., Yeh M.M., RA Fausto N.; RT "Platelet-derived growth factor C induces liver fibrosis, steatosis, and RT hepatocellular carcinoma."; RL Proc. Natl. Acad. Sci. U.S.A. 102:3389-3394(2005). RN [25] RP FUNCTION, AND INDUCTION. RX PubMed=16439802; DOI=10.1165/rcmb.2005-0309oc; RA Bosse Y., Thompson C., Stankova J., Rola-Pleszczynski M.; RT "Fibroblast growth factor 2 and transforming growth factor beta1 synergism RT in human bronchial smooth muscle cell proliferation."; RL Am. J. Respir. Cell Mol. Biol. 34:746-753(2006). RN [26] RP SUBCELLULAR LOCATION, AND SUMOYLATION. RX PubMed=16443219; DOI=10.1016/j.yexcr.2005.11.035; RA Reigstad L.J., Martinez A., Varhaug J.E., Lillehaug J.R.; RT "Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid RT tissue and cell lines."; RL Exp. Cell Res. 312:782-795(2006). RN [27] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=18055825; DOI=10.1167/iovs.07-0327; RA Li R., Maminishkis A., Wang F.E., Miller S.S.; RT "PDGF-C and -D induced proliferation/migration of human RPE is abolished by RT inflammatory cytokines."; RL Invest. Ophthalmol. Vis. Sci. 48:5722-5732(2007). RN [28] RP TISSUE SPECIFICITY. RX PubMed=17482170; DOI=10.1016/j.fertnstert.2007.02.031; RA Hwu Y.M., Li S.H., Lee R.K., Tsai Y.H., Yeh T.S., Lin S.Y.; RT "Increased expression of platelet-derived growth factor C messenger RT ribonucleic acid in uterine leiomyomata."; RL Fertil. Steril. 89:468-471(2008). RN [29] RP CLEAVAGE BY PLG. RX PubMed=18172073; DOI=10.1167/iovs.07-0776; RA Lei H., Velez G., Hovland P., Hirose T., Kazlauskas A.; RT "Plasmin is the major protease responsible for processing PDGF-C in the RT vitreous of patients with proliferative vitreoretinopathy."; RL Invest. Ophthalmol. Vis. Sci. 49:42-48(2008). CC -!- FUNCTION: Growth factor that plays an essential role in the regulation CC of embryonic development, cell proliferation, cell migration, survival CC and chemotaxis. Potent mitogen and chemoattractant for cells of CC mesenchymal origin. Required for normal skeleton formation during CC embryonic development, especially for normal development of the CC craniofacial skeleton and for normal development of the palate. CC Required for normal skin morphogenesis during embryonic development. CC Plays an important role in wound healing, where it appears to be CC involved in three stages: inflammation, proliferation and remodeling. CC Plays an important role in angiogenesis and blood vessel development. CC Involved in fibrotic processes, in which transformation of interstitial CC fibroblasts into myofibroblasts plus collagen deposition occurs. The CC CUB domain has mitogenic activity in coronary artery smooth muscle CC cells, suggesting a role beyond the maintenance of the latency of the CC PDGF domain. In the nucleus, PDGFC seems to have additional function. CC {ECO:0000269|PubMed:10806482, ECO:0000269|PubMed:10858496, CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11854040, CC ECO:0000269|PubMed:12032822, ECO:0000269|PubMed:15061151, CC ECO:0000269|PubMed:15372073, ECO:0000269|PubMed:15389578, CC ECO:0000269|PubMed:15728360, ECO:0000269|PubMed:15911618, CC ECO:0000269|PubMed:16439802, ECO:0000269|PubMed:18055825}. CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, CC and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB CC domain) with PLAT (via kringle domain). {ECO:0000269|PubMed:12598536, CC ECO:0000269|PubMed:15372073, ECO:0000269|PubMed:15911618}. CC -!- INTERACTION: CC Q9NRA1; P16234: PDGFRA; NbExp=3; IntAct=EBI-8833587, EBI-2861522; CC Q9NRA1-1; P16234-1: PDGFRA; NbExp=2; IntAct=EBI-15499301, EBI-15499330; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16443219}. CC Secreted {ECO:0000269|PubMed:10806482, ECO:0000269|PubMed:10858496, CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:15061151, CC ECO:0000269|PubMed:15372073, ECO:0000269|PubMed:15911618}. Nucleus CC {ECO:0000269|PubMed:16443219}. Cytoplasmic granule CC {ECO:0000269|PubMed:15061151}. Cell membrane CC {ECO:0000269|PubMed:16443219}. Note=Sumoylated form is predominant in CC the nucleus (PubMed:15247255). Stored in alpha granules in platelets CC (PubMed:15061151). {ECO:0000269|PubMed:16443219}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9NRA1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NRA1-2; Sequence=VSP_034703; CC Name=3; CC IsoId=Q9NRA1-3; Sequence=VSP_034701, VSP_034702; CC Name=4; CC IsoId=Q9NRA1-4; Sequence=VSP_047606; CC -!- TISSUE SPECIFICITY: Expressed in the fallopian tube, vascular smooth CC muscle cells in kidney, breast and colon and in visceral smooth muscle CC of the gastrointestinal tract. Highly expressed in retinal pigment CC epithelia. Expressed in medulloblastoma. In the kidney, constitutively CC expressed in parietal epithelial cells of Bowman's capsule, tubular CC epithelial cells and in arterial endothelial cells (at protein level). CC Highly expressed in the platelets, prostate, testis and uterus. Higher CC expression is observed in uterine leiomyomata. Weaker expression in the CC spleen, thymus, heart, pancreas, liver, ovary cells and small CC intestine, and negligible expression in the colon and peripheral blood CC leukocytes. {ECO:0000269|PubMed:10806482, ECO:0000269|PubMed:11004490, CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11342471, CC ECO:0000269|PubMed:11854040, ECO:0000269|PubMed:12176024, CC ECO:0000269|PubMed:15061151, ECO:0000269|PubMed:17482170, CC ECO:0000269|PubMed:18055825}. CC -!- DEVELOPMENTAL STAGE: In the fetal kidney, detected in the developing CC mesangium, ureteric bud epithelium and the undifferentiated mesenchyme CC (at protein level). {ECO:0000269|PubMed:12707385}. CC -!- INDUCTION: Up-regulated by EWS-FLI1 chimeric transcription factor in CC tumor derived cells. Up-regulated in podocytes and interstitial cells CC after injury/activation of these cells. FGF2 activates PDGFC CC transcription via EGR1. Up-regulated by TGFB1 in concert with FGF2. CC {ECO:0000269|PubMed:11313995, ECO:0000269|PubMed:12707385, CC ECO:0000269|PubMed:15247255, ECO:0000269|PubMed:16439802}. CC -!- PTM: Proteolytic removal of the N-terminal CUB domain releasing the CC core domain is necessary for unmasking the receptor-binding epitopes of CC the core domain. Cleavage after basic residues in the hinge region CC (region connecting the CUB and growth factor domains) gives rise to the CC receptor-binding form. Cleaved by PLAT and PLG. CC -!- PTM: Sumoylated with SUMO1. {ECO:0000269|PubMed:16443219}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11854040}. CC -!- MISCELLANEOUS: A lower molecular weight form (around 43 kDa) is present CC in patients with papillary thyroid carcinoma. CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF091434; AAF00049.1; -; mRNA. DR EMBL; AB033831; BAB03266.1; -; mRNA. DR EMBL; AF244813; AAF80597.1; -; mRNA. DR EMBL; AF260738; AAK51637.1; -; mRNA. DR EMBL; AM922296; CAP58278.1; -; mRNA. DR EMBL; AY358493; AAQ88857.1; -; mRNA. DR EMBL; AK300480; BAG62196.1; -; mRNA. DR EMBL; AC092608; AAY40906.1; -; Genomic_DNA. DR EMBL; AC093325; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471056; EAX04874.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04875.1; -; Genomic_DNA. DR EMBL; BC136662; AAI36663.1; -; mRNA. DR CCDS; CCDS3795.1; -. [Q9NRA1-1] DR RefSeq; NP_057289.1; NM_016205.2. [Q9NRA1-1] DR RefSeq; XP_016863945.1; XM_017008456.1. DR AlphaFoldDB; Q9NRA1; -. DR SMR; Q9NRA1; -. DR BioGRID; 121032; 12. DR ComplexPortal; CPX-2879; Platelet-derived growth factor CC complex. DR ComplexPortal; CPX-2887; PDGF receptor alpha - PDGF-CC complex. DR ComplexPortal; CPX-2888; PDGF receptor alpha-beta - PDGF-CC complex. DR ComplexPortal; CPX-2891; PDGF receptor beta - PDGF-CC complex. DR DIP; DIP-59339N; -. DR IntAct; Q9NRA1; 5. DR STRING; 9606.ENSP00000422464; -. DR GlyCosmos; Q9NRA1; 2 sites, No reported glycans. DR GlyGen; Q9NRA1; 2 sites. DR iPTMnet; Q9NRA1; -. DR PhosphoSitePlus; Q9NRA1; -. DR BioMuta; PDGFC; -. DR DMDM; 205830662; -. DR EPD; Q9NRA1; -. DR MassIVE; Q9NRA1; -. DR PaxDb; 9606-ENSP00000422464; -. DR PeptideAtlas; Q9NRA1; -. DR ProteomicsDB; 5147; -. DR ProteomicsDB; 82318; -. [Q9NRA1-1] DR ProteomicsDB; 82319; -. [Q9NRA1-2] DR ProteomicsDB; 82320; -. [Q9NRA1-3] DR Pumba; Q9NRA1; -. DR Antibodypedia; 28096; 380 antibodies from 29 providers. DR DNASU; 56034; -. DR Ensembl; ENST00000422544.2; ENSP00000410048.2; ENSG00000145431.11. [Q9NRA1-2] DR Ensembl; ENST00000502773.6; ENSP00000422464.1; ENSG00000145431.11. [Q9NRA1-1] DR GeneID; 56034; -. DR KEGG; hsa:56034; -. DR MANE-Select; ENST00000502773.6; ENSP00000422464.1; NM_016205.3; NP_057289.1. DR UCSC; uc003iph.3; human. [Q9NRA1-1] DR AGR; HGNC:8801; -. DR CTD; 56034; -. DR DisGeNET; 56034; -. DR GeneCards; PDGFC; -. DR HGNC; HGNC:8801; PDGFC. DR HPA; ENSG00000145431; Tissue enhanced (parathyroid). DR MIM; 608452; gene. DR neXtProt; NX_Q9NRA1; -. DR OpenTargets; ENSG00000145431; -. DR PharmGKB; PA33146; -. DR VEuPathDB; HostDB:ENSG00000145431; -. DR eggNOG; ENOG502QUUR; Eukaryota. DR GeneTree; ENSGT00940000158645; -. DR HOGENOM; CLU_037859_0_0_1; -. DR InParanoid; Q9NRA1; -. DR OMA; MCVVIQT; -. DR OrthoDB; 3908391at2759; -. DR PhylomeDB; Q9NRA1; -. DR TreeFam; TF332130; -. DR PathwayCommons; Q9NRA1; -. DR Reactome; R-HSA-186797; Signaling by PDGF. [Q9NRA1-1] DR SignaLink; Q9NRA1; -. DR SIGNOR; Q9NRA1; -. DR BioGRID-ORCS; 56034; 16 hits in 1148 CRISPR screens. DR ChiTaRS; PDGFC; human. DR GeneWiki; PDGFC; -. DR GenomeRNAi; 56034; -. DR Pharos; Q9NRA1; Tbio. DR PRO; PR:Q9NRA1; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q9NRA1; Protein. DR Bgee; ENSG00000145431; Expressed in parotid gland and 199 other cell types or tissues. DR ExpressionAtlas; Q9NRA1; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl. DR GO; GO:0060348; P:bone development; IEA:Ensembl. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; TAS:UniProtKB. DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl. DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IBA:GO_Central. DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR CDD; cd00041; CUB; 1. DR CDD; cd00135; PDGF; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 1. DR InterPro; IPR000859; CUB_dom. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR000072; PDGF/VEGF_dom. DR InterPro; IPR035914; Sperma_CUB_dom_sf. DR PANTHER; PTHR11633; PLATELET-DERIVED GROWTH FACTOR; 1. DR PANTHER; PTHR11633:SF5; PLATELET-DERIVED GROWTH FACTOR C; 1. DR Pfam; PF00431; CUB; 1. DR Pfam; PF00341; PDGF; 1. DR SMART; SM00042; CUB; 1. DR SMART; SM00141; PDGF; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 1. DR PROSITE; PS01180; CUB; 1. DR PROSITE; PS50278; PDGF_2; 1. DR Genevisible; Q9NRA1; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues; KW Cytoplasm; Developmental protein; Disulfide bond; Glycoprotein; KW Growth factor; Membrane; Mitogen; Nucleus; Reference proteome; Secreted; KW Signal; Ubl conjugation. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..345 FT /note="Platelet-derived growth factor C, latent form" FT /id="PRO_0000343871" FT CHAIN ?..345 FT /note="Platelet-derived growth factor C, receptor-binding FT form" FT /id="PRO_0000343872" FT DOMAIN 46..163 FT /note="CUB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT SITE 225..226 FT /note="Cleavage" FT SITE 231..232 FT /note="Cleavage" FT /evidence="ECO:0000255" FT SITE 234..235 FT /note="Cleavage" FT /evidence="ECO:0000255" FT CARBOHYD 25 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 55 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT DISULFID 104..124 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DISULFID 250..294 FT /evidence="ECO:0000305|PubMed:12598536" FT DISULFID 274 FT /note="Interchain (with C-286)" FT /evidence="ECO:0000305|PubMed:12598536" FT DISULFID 280..335 FT /evidence="ECO:0000305|PubMed:12598536" FT DISULFID 286 FT /note="Interchain (with C-274)" FT /evidence="ECO:0000305|PubMed:12598536" FT DISULFID 287..337 FT /evidence="ECO:0000305|PubMed:12598536" FT VAR_SEQ 1..163 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.5" FT /id="VSP_047606" FT VAR_SEQ 155..167 FT /note="GFCIHYNIVMPQF -> SNRGGKIIQLHTS (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_034701" FT VAR_SEQ 168..345 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_034702" FT VAR_SEQ 244..306 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_034703" FT MUTAGEN 124 FT /note="C->S: Loss of mitogenic activity of CUB domain in FT coronary artery smooth muscle cells." FT /evidence="ECO:0000269|PubMed:11854040" FT MUTAGEN 231 FT /note="R->A: Essential for cleavage by PLAT." FT /evidence="ECO:0000269|PubMed:15911618" FT MUTAGEN 232 FT /note="K->A: Not essential for cleavage by PLAT." FT /evidence="ECO:0000269|PubMed:15911618" FT MUTAGEN 234 FT /note="R->A: Not essential for cleavage by PLAT." FT /evidence="ECO:0000269|PubMed:15911618" FT CONFLICT 9 FT /note="L -> V (in Ref. 3; AAF80597)" FT /evidence="ECO:0000305" FT CONFLICT 18 FT /note="Q -> R (in Ref. 3; AAF80597)" FT /evidence="ECO:0000305" SQ SEQUENCE 345 AA; 39029 MW; CDE9E51F40633E78 CRC64; MSLFGLLLLT SALAGQRQGT QAESNLSSKF QFSSNKEQNG VQDPQHERII TVSTNGSIHS PRFPHTYPRN TVLVWRLVAV EENVWIQLTF DERFGLEDPE DDICKYDFVE VEEPSDGTIL GRWCGSGTVP GKQISKGNQI RIRFVSDEYF PSEPGFCIHY NIVMPQFTEA VSPSVLPPSA LPLDLLNNAI TAFSTLEDLI RYLEPERWQL DLEDLYRPTW QLLGKAFVFG RKSRVVDLNL LTEEVRLYSC TPRNFSVSIR EELKRTDTIF WPGCLLVKRC GGNCACCLHN CNECQCVPSK VTKKYHEVLQ LRPKTGVRGL HKSLTDVALE HHEECDCVCR GSTGG //